scholarly journals Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Raffaele Nardone ◽  
Yvonne Höller ◽  
Monica Storti ◽  
Monica Christova ◽  
Frediano Tezzon ◽  
...  
Keyword(s):  
Thiamine Deficiency ◽  
Cortical Cell ◽  
Cell Loss ◽  
Brain Regions ◽  
Experimental Models ◽  
Neurological Sequela ◽  
Thalamic Nuclei ◽  
Chronic Alcoholic ◽  
Ethanol Abuse ◽  
And Function

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

scholarly journals Increased Densities of Binding Sites for the “Peripheral-Type” Benzodiazepine Receptor Ligand [3H]PK11195 in Vulnerable Regions of the Rat Brain in Thiamine Deficiency Encephalopathy

1994 ◽  
Vol 14 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Dorothy K. Leong ◽  
Oanh Le ◽  
Luis Oliva ◽  
Roger F. Butterworth
Keyword(s):  
Binding Sites ◽  
Thiamine Deficiency ◽  
Neuronal Cell ◽  
Neuronal Loss ◽  
Benzodiazepine Receptor ◽  
Cell Loss ◽  
Brain Regions ◽  
Inferior Olivary Nucleus ◽  
Neuronal Cell Loss ◽  
Peripheral Type

Quantitative receptor autoradiography was used to evaluate the density of high-affinity binding sites for the “peripheral-type” benzodiazepine receptor (PTBR) ligand [3H]PK11195 in brain regions of the rat at different stages of pyrithiamine-induced thiamine deficiency encephalopathy, an experimental model of the Wernicke-Korsakoff syndrome (WKS). Assessment of the density of [3H]PK11195 binding sites in thiamine-deficient animals showing no neurologic signs of thiamine deficiency encephalopathy, and revealed no significant alterations compared with pair-fed control animals in any brain region studied. Densities of [3H]PK11195 binding sites were, however, significantly increased in brain regions of the rat at the symptomatic stage, where increased densities were seen in the inferior colliculus (233% increase, p < 0.001), inferior olivary nucleus (154% increase, p < 0.001) and thalamus (up to 107% increase, p < 0.001). Histologic studies of these same brain regions revealed evidence of neuronal cell loss and concomitant gliosis. Densities of [3H]PK11195 binding sites in nonvulnerable brain regions that showed no histologic evidence of neuronal loss, such as the cerebral cortex, hippocampus, and caudate-putamen, were not significantly different from those in control animals. Increased densities of binding sites for the PTBR ligand probably reflect glial proliferation and are consistent with an excitotoxic mechanism in the pathogenesis of neuronal cell loss in thiamine deficiency encephalopathy. Positron emission tomography (PET) using [11C]PK11195 could offer a potentially useful diagnostic tool in WKS in humans.

scholarly journals Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming

2021 ◽  
Vol 7 (15) ◽  
pp. eabe8978
Author(s):  
Álvaro Herrero-Navarro ◽  
Lorenzo Puche-Aroca ◽  
Verónica Moreno-Juan ◽  
Alejandro Sempere-Ferràndez ◽  
Ana Espinosa ◽  
...  
Keyword(s):  
Molecular Diversity ◽  
Regional Identity ◽  
Brain Regions ◽  
Molecular Signature ◽  
Specific Gene ◽  
Thalamic Nuclei ◽  
Brain Repair ◽  
Cell Diversity ◽  
Regional Specificity ◽  
Epigenetic Signatures

Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.

scholarly journals Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  
Keyword(s):  
Neural Development ◽  
Protein Level ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Pathophysiological Mechanism ◽  
Brain Disorders ◽  
Spine Density ◽  
Genes Encoding ◽  
High Level ◽  
And Function

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.

scholarly journals Differential Promotion of Glutamate Transporter Expression and Function by Glucocorticoids in Astrocytes from Various Brain Regions

2005 ◽  
Vol 280 (41) ◽  
pp. 34924-34932 ◽  
Author(s):  
Jürgen Zschocke ◽  
Nadhim Bayatti ◽  
Albrecht M. Clement ◽  
Heidrun Witan ◽  
Maciej Figiel ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Brain Regions ◽  
And Function ◽  
Transporter Expression

scholarly journals Experimental Models to Study COVID-19 Effect in Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 91
Author(s):  
Rishi Man Chugh ◽  
Payel Bhanja ◽  
Andrew Norris ◽  
Subhrajit Saha
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Drug Efficacy ◽  
Cell Loss ◽  
Experimental Models ◽  
Model Systems ◽  
Virus Infectivity ◽  
Ex Vivo Model ◽  
Global Pandemic ◽  
The Impact

The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addition to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic consequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs. In this review, we discuss ex vivo experimental models available to study the effect of COVID-19 on tissue stem cells.

Animal Models of Down Syndrome

2021 ◽  
Author(s):  
Anna J. Moyer ◽  
Roger H. Reeves
Keyword(s):  
Down Syndrome ◽  
Cognitive Impairment ◽  
Intellectual Disability ◽  
Animal Models ◽  
Brain Regions ◽  
Laboratory Mice ◽  
Tremendous Progress ◽  
New Treatments ◽  
And Function ◽  
Early Developmental

Is intellectual disability a treatable feature of persons with Down syndrome? Researchers have made tremendous progress in the last 30 years, from creating the first mouse model of Down syndrome to completing the first major clinical trial for cognitive impairment in people with Down syndrome. Until recently, normalizing brain development and function seemed too lofty a goal, and indeed, even proposing a candidate therapy requires answering a number of difficult questions. How does trisomy 21, a molecular diagnosis, cause the clinical phenotypes of Down syndrome? When, where, and how do trisomic genes act to disrupt normal development and which genes are involved with which outcomes? Which brain regions and behaviors are most impaired? Is there an early developmental window of time during which treatments are most effective? This article discusses how animal models such as laboratory mice can be used to understand intellectual disability and to develop new treatments for cognitive impairment.

scholarly journals Altered folate binding protein expression and folate delivery are associated with congenital hydrocephalus in the hydrocephalic Texas rat

2018 ◽  
Vol 39 (10) ◽  
pp. 2061-2073 ◽  
Author(s):  
Alicia Requena Jimenez ◽  
Naila Naz ◽  
Jaleel A Miyan
Keyword(s):  
Folate Receptor ◽  
Cortical Cell ◽  
Regulatory Function ◽  
Folate Binding Protein ◽  
In Vitro Proliferation ◽  
Cycle Arrest ◽  
Csf Levels ◽  
And Function

Hydrocephalus (HC) is an imbalance in cerebrospinal fluid (CSF) secretion/absorption resulting in fluid accumulation within the brain with consequential pathophysiology. Our research has identified a unique cerebral folate system in which depletion of CSF 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is associated with cortical progenitor cell-cycle arrest in hydrocephalic Texas (H-Tx) rats. We used tissue culture, immunohistochemistry, in-situ PCR and RT-PCR and found that the in-vitro proliferation of arachnoid cells is highly folate-dependent with exacerbated proliferation occurring in hydrocephalic CSF that has low FDH but high folate-receptor-alpha (FRα) and folate. Adding FDH to this CSF prevented aberrant proliferation indicating a regulatory function of FDH on CSF folate concentration. Arachnoid cells have no detectable mRNA for FRα or FDH, but FDH mRNA is found in the choroid plexus (CP) and CSF microvesicles. Co-localization of FDH, FRα and folate suggests important functions of FDH in cerebral folate transport, buffering and function. In conclusion, abnormal CSF levels of FDH, FRα and folate inhibit cortical cell proliferation but allow uncontrolled arachnoid cell division that should increase fluid absorption by increasing the arachnoid although this fails in the hydrocephalic brain. FDH appears to buffer available folate to control arachnoid proliferation and function.

scholarly journals From Mice to Mainframes: Experimental Models for Investigation of the Intracardiac Nervous System

2021 ◽  
Vol 8 (11) ◽  
pp. 149
Author(s):  
Matthew R. Stoyek ◽  
Luis Hortells ◽  
T. Alexander Quinn
Keyword(s):  
Cardiovascular Disease ◽  
Nervous System ◽  
Computational Models ◽  
Neural Circuitry ◽  
Experimental Models ◽  
Incomplete Knowledge ◽  
Fundamental Understanding ◽  
Health And Disease ◽  
And Function ◽  
Intracardiac Nervous System

The intracardiac nervous system (IcNS), sometimes referred to as the “little brain” of the heart, is involved in modulating many aspects of cardiac physiology. In recent years our fundamental understanding of autonomic control of the heart has drastically improved, and the IcNS is increasingly being viewed as a therapeutic target in cardiovascular disease. However, investigations of the physiology and specific roles of intracardiac neurons within the neural circuitry mediating cardiac control has been hampered by an incomplete knowledge of the anatomical organisation of the IcNS. A more thorough understanding of the IcNS is hoped to promote the development of new, highly targeted therapies to modulate IcNS activity in cardiovascular disease. In this paper, we first provide an overview of IcNS anatomy and function derived from experiments in mammals. We then provide descriptions of alternate experimental models for investigation of the IcNS, focusing on a non-mammalian model (zebrafish), neuron-cardiomyocyte co-cultures, and computational models to demonstrate how the similarity of the relevant processes in each model can help to further our understanding of the IcNS in health and disease.

scholarly journals A Neural Model of Intrinsic and Extrinsic Hippocampal Theta Rhythms: Anatomy, Neurophysiology, and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Stephen Grossberg
Keyword(s):  
Entorhinal Cortex ◽  
Category Learning ◽  
Neural Model ◽  
Brain Regions ◽  
Beta Oscillations ◽  
Emotional Processes ◽  
Theoretical Synthesis ◽  
Multiple Species ◽  
And Function ◽  
Hippocampal Theta

This article describes a neural model of the anatomy, neurophysiology, and functions of intrinsic and extrinsic theta rhythms in the brains of multiple species. Topics include how theta rhythms were discovered; how theta rhythms organize brain information processing into temporal series of spatial patterns; how distinct theta rhythms occur within area CA1 of the hippocampus and between the septum and area CA3 of the hippocampus; what functions theta rhythms carry out in different brain regions, notably CA1-supported functions like learning, recognition, and memory that involve visual, cognitive, and emotional processes; how spatial navigation, adaptively timed learning, and category learning interact with hippocampal theta rhythms; how parallel cortical streams through the lateral entorhinal cortex (LEC) and the medial entorhinal cortex (MEC) represent the end-points of the What cortical stream for perception and cognition and the Where cortical stream for spatial representation and action; how the neuromodulator acetylcholine interacts with the septo-hippocampal theta rhythm and modulates category learning; what functions are carried out by other brain rhythms, such as gamma and beta oscillations; and how gamma and beta oscillations interact with theta rhythms. Multiple experimental facts about theta rhythms are unified and functionally explained by this theoretical synthesis.

scholarly journals Forced Normalization Revisited: New Concepts About a Paradoxical Phenomenon

2021 ◽  
Vol 15 ◽  
Author(s):  
José Augusto Bragatti
Keyword(s):  
Imaging Techniques ◽  
Brain Regions ◽  
Experimental Models ◽  
Psychotic Symptoms ◽  
Resting State Networks ◽  
Epileptiform Discharges ◽  
New Concepts ◽  
Forced Normalization ◽  
Electrical Stimuli ◽  
Patients With Epilepsy

The phenomenon of Forced Normalization (FN) was first described by Landolt in 1953, who described the disappearance of epileptiform discharges in the EEG of patients with epilepsy, concomitant with the development of psychotic symptoms. Later, Tellenbach coined the term “alternative psychosis” referring specifically to the alternation between clinical phenomena. Finally, in 1991, Wolf observed a degenerative process involved in the phenomenon, which he called “paradoxical normalization.” Initially, FN was explained through experimental models in animals and the demonstration of the kindling phenomenon, in its electrical and pharmacological subdivisions. At this stage of research on the epileptic phenomenon, repetitive electrical stimuli applied to susceptible regions of the brain (hippocampus and amygdala) were considered to explain the pathophysiological basis of temporal lobe epileptogenesis. Likewise, through pharmacological manipulation, especially of dopaminergic circuits, psychiatric comorbidities began to find their basic mechanisms. With the development of new imaging techniques (EEG/fMRI), studies in the area started to focus on the functional connectivity (FC) of different brain regions with specific neuronal networks, which govern emotions. Thus, a series of evidence was produced relating the occurrence of epileptic discharges in the limbic system and their consequent coactivation and deactivation of these resting-state networks. However, there are still many controversies regarding the basic mechanisms of network alterations related to emotional control, which will need to be studied with a more homogeneous methodology, in order to try to explain this interesting neuropsychiatric phenomenon with greater accuracy.

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